This application addresses broad Challenge Area (4) Clinical Research and specific Challenge Topic, 04-HL- 104: Perform secondary analyses of existing data to answer important clinical and preventive medicine research questions. According to the Surgeon General's 2008 Call to Action to Prevent Deep Venous Thrombosis and Pulmonary Embolism, over 300,000 Americans each year suffer from venous thromboembolism (VTE), with potentially over 100,000 fatalities per year. VTE is approximately 1.5-fold more common in African-Americans as compared to European-Americans;the reasons for this disparity being unclear. The greatest difficulty in studying the reasons for this disparity in incidence is due in great part to a paucity of African-Americans in research studies of VTE to date, especially where risk factors are measured before the VTE event. The purpose of this Challenge Grant is to ascertain and validate venous thromboembolism (VTE) events in the REasons for Geographic and Racial Differences in Stroke Study (REGARDS), a prospective national cohort study investigating geographic and racial disparities in stroke incidence and risk-factors in the United States and combine the data with the Longitudinal Investigation of Thromboembolism Etiology (LITE) in order to obtain a prospective cohort study with sufficient VTE events among African-Americans and European- Americans to evaluate racial disparities in VTE incidence in the United States. The LITE study is a prospective cohort study of 21,680 individuals from the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study with 726 VTE events (though only 224 among African-Americans). The resulting harmonized cohort combining both LITE and REGARDS will consist of 51,848 individuals, of whom 17,713 are African-Americans. We anticipate a combined total 1,292 incident VTE, 492 of which will be among African-Americans. Each of these cohorts (REGARDS, CHS, ARIC) has extensive baseline demographic, anthropometric, socio- economic, and medical history recorded, a baseline stored blood and urine repository, as well as follow-up events information including cardiovascular diseases, hospitalizations, and death. Risk factors were measured and validated rather than self-reported in each cohort. By accomplishing our specific aims, we will be able to evaluate the risk factors which mediate the racial difference in VTE incidence seen in the United States. This project offers not only the opportunity to evaluate traditional risk factors for VTE, such as cancer, surgery, obesity, and medical conditions, but the opportunity to study novel risk factors such as nutrition, physical activity, and cognitive function. Results will lead to a follow- up proposal to obtain funding to evaluate novel biomarkers of VTE risk such as factor VIII, von Willebrand factor levels, and genetic factors in African-Americans versus European-Americans. By understanding the reasons for the racial disparity in VTE incidence, we will be able to propose interventions or further studies to address reducing this disparity. The team assembled for this project is uniquely suited to do this research. Dr. N. Zakai (the Principal Investigator for this Grant) is a hematologist and has worked on the LITE study and on investigating racial disparities in the REGARDS study. Dr. M. Cushman, a hematologist, is the site PI for the LITE study and the REGARDS central laboratory at the University of Vermont. Dr. A. Folsom is the overall PI of LITE at the University of Minnesota. For REGARDS, Dr. G. Howard, a biostatistician, is the overall PI of REGARDS and an expert in racial disparities. Dr. L. McClure is the lead biostatistician for REGARDS and very familiar with the cohort. Dr. S. Judd is an expert on nutritional assessment in cohort studies, and Dr. V. Wadley is an expert on cognitive assessment. Dr. M. Safford is head of the clinical outcomes unit in REGARDS and PI of the NHLBI- funded REGARDS ancillary study assessing racial disparities in myocardial infarction. African-Americans have an approximately 30% to 60% increased incidence of venous thromboembolism (VTE) for unknown reasons. The main limitation to studying this disparity is the paucity of African-Americans in most large-scale epidemiological studies. The purpose of this Challenge Grant is to ascertain and validate VTE events in the REasons for Geographic and Racial Differences in Stroke Study (REGARDS), a prospective national cohort study investigating geographic and racial disparities in stroke incidence and risk-factors in the United States and combine the data with the Longitudinal Investigation of Thromboembolism Etiology (LITE) in order to obtain a prospective cohort study with sufficient VTE events among African-Americans and European-Americans to evaluate racial disparities in VTE in the United States. Though understanding the reasons for this disparity we can begin to formulate public health policies to address this disparity.